The candidate received her DVM (1984), completed a residency in Small Animal Neurology/Neurosurgery (1985-88), and had a productive PhD (1988-92) and postdoctoral training program (1993-94) in neuroscience-related programs. Due to her spouse having tenure in his professional position, she took a predominantly teaching position at a small local college for the past 7 years. As of April 2001, the candidate returned to a full-time, tenure-track faculty position at Auburn University, a major research university in the state of AL, and is once again pursuing her research interests in neuroscience. The candidate's long term career goals are to establish an independent research laboratory, with extramural funding, focusing on the role of astrocytes in central nervous system (CNS) disorders linked to metabolic diseases and neurotoxicities. Her immediate goals are to acquire proper mentoring and technical skills to strengthen her research capabilities, and to collect preliminary data to write a major research grant. There is a strong diabetes core research group in her department interested in expanding studies to include effects on the CNS. Diabetes mellitus has been declared an epidemic in the United States by the Centers for Disease Control. Individuals with type I and type 2 diabetes are at increased risk for CNS disorders such as dementia, cognitive impairment, seizures, and stroke. The cellular mechanisms responsible for the increased risk of these disorders are incompletely understood. We hypothesize that diabetes induces its detrimental effects on the CNS, in part, through disruption of astrocyte numbers and/or activity, leading to disturbances in normal glutamate regulation and ultimately dysfunction and demise of neurons. Glutamate is the major excitatory neurotransmitter in the CNS, which in excess is neurotoxic, and astrocytes are the major regulators of extracellular glutamate concentrations. Preliminary data included in this application demonstrates that diabetes induces a statistically significant decrease in glial fibrillary acidic protein, a protein used to assess astrocyte activity, in the cerebral cortex and hippocampus of streptozotocin-induced diabetic rats after 6 weeks of diabetes. The specific objective of this research proposal is to determine the effects of diabetes on astrocyte regulation of glutamate uptake in select brain regions. The following Specific Aims will be examined: 1) Determine the effects of diabetes on astrocyte numbers/activity and astrocyte glutamate transporter levels, 2) determine the effects of diabetes on astrocyte glutamate uptake and astrocyte N+'K+ATPase activity, and 3) determine the effects of insulin therapy on diabetes-induced alterations of astrocyte activity and regulation of glutamate uptake. In summary, this application targets the role of altered astrocyte activity and glutamate uptake in diabetes-induced CNS disorders.